A social partner’s emotions communicate important information about their motives and intentions. However, people may discount emotional information that they believe their partner has regulated with the strategic intention of exerting social influence. Across two studies, we investigated interpersonal effects of communicated guilt and perceived strategic regulation in trust games. Results showed that communicated guilt mitigated negative effects of trust violations on interpersonal judgements and behaviour. Further, perceived strategic regulation reduced guilt’s positive effects. These findings suggest that people take emotion-regulation (...) motives into account when responding to emotion communication. (shrink)

Workplace ethics perceptions drive ethical behaviors, but our understanding of how context shapes the nature of this relationship is limited. Consequently, this article uses contingency theory to explore how perceptions of ethical priorities in the workplace—ethical work climate (EWC)—are differentially associated with ethical behavior based on the broader context. Specifically, we meta-analytically test theoretically relevant cultural values (i.e., collectivism, power distance) and work context factors (i.e., consequence of errors, job autonomy) as moderators of the connection between EWC perceptions and ethical (...) behavior. Our findings reveal that while higher power-distance societal contexts strengthen the connection between EWC perceptions and ethical behavior, work contexts with higher autonomy _weaken_ the connection. We found mixed support for collectivism as a contextual moderator, with results supporting theoretical expectations with one cultural conceptualization but not another. Contrary to expectations, the consequences of errors in work contexts did not moderate the association between EWC perceptions and ethical behavior. Taken together, this meta-analytic investigation highlights the meaningful role of the broader organizational context as a potential boundary condition for the influence of EWC perceptions on ethical behavior. (shrink)

According to Brehm's intensity of emotion theory, if an emotion has motivational properties, its intensity should be non-monotonically affected by factors similar to those determining the intensity of motivational states. These factors are called deterrents. In the case of emotion, one category of deterrents consists of factors that can potentially interfere with feeling the emotion, such as reasons for not feeling the emotion. Two experiments were carried out to examine whether happiness is a motivational state and, thus, if its intensity (...) is non-monotonically determined by the importance of reasons for not feeling happy. We expected happiness to be reduced by a low importance reason for not feeling happy, to remain high in the presence of a moderately important reason, and to be reduced or eliminated by a very important reason. Both experiments supported the cubic function that results from these expectations, and when the results of the two studies were combined, each of the individual legs of the cubic function was found to be reliable along with the cubic function itself. The theoretical implications of these results are discussed. (shrink)

People judge that an individual who attempts to harm someone but fails should be blamed and punished more when they imagine how things could have turned out worse, compared to when they imagine how things could have turned out the same, or when they think only about what happened. This moral counterfactual amplification effect occurs when people believe the protagonist had no reason for the attempt to harm, and not when the protagonist had a reason, as Experiment 1 shows. It (...) occurs for intentional failed attempts to harm and also for accidental near-misses, as Experiment 2 shows, but not for failed attempts in which the harm occurs anyway by another cause, for both general judgments about the event and specific judgments about the individual's actions, as Experiments 3 and 4 show. The implications for understanding the role of counterfactual thoughts in moral judgement are discussed. (shrink)

Parkinson's Disease (PD) is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms generally come on slowly over time. Early in the disease, the most obvious are shaking, rigidity, slowness of movement, and difficulty with walking. Doctors do not know what causes it and finds difficulty in early diagnosing the presence of Parkinson’s disease. An artificial neural network system with back propagation algorithm is presented in this paper for helping doctors (...) in identifying PD. Previous research with regards to predict the presence of the PD has shown accuracy rates up to 93% [1]; however, accuracy of prediction for small classes is reduced. The proposed design of the neural network system causes a significant increase of robustness. It is also has shown that networks recognition rates reached 100%. (shrink)

PURPOSE: To evaluate the effects of social support on comprehension and recall of consent form information in a study of Parkinson disease patients and their caregivers.DESIGN and METHODS: Comparison of comprehension and recall outcomes among participants who read and signed the consent form accompanied by a family member/friend versus those of participants who read and signed the consent form unaccompanied. Comprehension and recall of consent form information were measured at one week and one month respectively, using Part A of (...) the Quality of Informed Consent Questionnaire .RESULTS: The mean age of the sample of 143 participants was 71 years . Analysis of covariance was used to compare QuIC scores between the intervention group and control group . In the 1-week model, no statistically significant intervention effect was found . However, the intervention status by patient status interaction was statistically significant . In the 1-month model, no statistically significant intervention effect was found . Again, however, the intervention status by patient status interaction was statistically significant . At both time periods, intervention group patients scored higher on the QuIC than did intervention group caregivers, and control group patients scored lower on the QuIC than did control group caregivers.IMPLICATIONS: Social support played a significant role in enhancing comprehension and recall of consent form information among patients. (shrink)

BACKGROUND: Hallucinations and delusions that complicate Parkinson’s disease could lead to nursing home placement and are linked to increased mortality. Cognitive impairments are typically associated with the presence of hallucinations but there are no data regarding whether such a relationship exists with delusions. OBJECTIVE: We hypothesized that hallucinations would be associated with executive and visuospatial disturbance. An exploratory examination of cognitive correlates of delusions was also completed to address the question of whether they differ from hallucinations. METHODS: 144 PD (...) subjects completed a neuropsychological battery to assess cognition and the SAPS to examine psychosis. Correlational analyses assessed associations between hallucinations and delusions with cognitive domains. RESULTS: 48 subjects reported psychotic symptoms: 25 experienced hallucinations without delusions, 23 had symptoms dominated by delusions. Severity and/or number of hallucination subtypes were significantly correlated with lower scores in language, memory, attention, executive functioning, and visuospatial ability. Correlations with delusions were non-significant. Tests of differences in the size of the correlations between groups revealed a significant relationship between language and visuospatial performance with hallucinations. CONCLUSIONS: Cognitive correlates of hallucinations and delusions appear to be different in PD, suggesting distinct pathogenic mechanisms and possibly anatomical substrates. Hence, delusions may not share the same associations with dementia as hallucinations. Since this is a new finding, further studies will be needed to confirm our results. (shrink)

Stem cells are likely to be used as an alternate source of biological material for neural transplantation to treat Parkinson’s disease in the not too distant future. Among the several ethical criteria that must be fulfilled before proceeding with clinical research, a favourable benefit to risk ratio must be obtained. The potential benefits to the participant and to society are evaluated relative to the risks in an attempt to offer the participants a reasonable choice. Through examination of preclinical studies (...) transplanting stem cells in animals and the transplantation of fetal tissue in patients with Parkinson’s disease, a current set of potential benefits and risks for neural transplantation of stem cells in clinical research of Parkinson’s disease are derived. The potential benefits to research participants undergoing stem cell transplantation are relief of parkinsonian symptoms and decreasing doses of parkinsonian drugs. Transplantation of stem cells as a treatment for Parkinson’s disease may benefit society by providing knowledge that can be used to help determine better treatments in the future. The risks to research participants undergoing stem cell transplantation include tumour formation, inappropriate stem cell migration, immune rejection of transplanted stem cells, haemorrhage during neurosurgery and postoperative infection. Although some of these risks are general to neurosurgical transplantation and may not be reduced for participants, the potential risk of tumour formation and inappropriate stem cell migration must be minimised before obtaining a favourable potential benefit to risk calculus and to provide participants with a reasonable choice before they enrol in clinical studies. (shrink)

Deep brain stimulation of the subthalamic nucleus or the globus pallidus is an established treatment for Parkinson’s disease that yields a marked and lasting improvement of motor symptoms. Yet, DBS benefit on gait disturbances in PD is still debated and can be a source of dissatisfaction and poor quality of life. Gait disturbances in PD encompass a variety of clinical manifestations and rely on different pathophysiological bases. While gait disturbances arising years after DBS surgery can be related to disease (...) progression, early impairment of gait may be secondary to treatable causes and benefits from DBS reprogramming. In this review, we tackle the issue of gait disturbances in PD patients with DBS by discussing their neurophysiological basis, providing a detailed clinical characterization, and proposing a pragmatic programming approach to support their management. (shrink)

Idiopathic Parkinson’s disease impairs working memory, but the exact nature of this deficit in terms of the underlying cognitive mechanisms is not well understood. In this study patients with mild clinical symptoms of PD were compared with matched healthy control subjects on a computerized battery of tests designed to assess spatial working memory and verbal working memory. In the spatial working memory task, subjects were required to recall a sequence of four locations. The verbal working memory task was methodologically (...) identical except for the modality of the stimuli used, requiring subjects to orally recall a sequence of six digits. In either case, half of the sequences were structured in a way that allowed ‘chunking’, while others were unstructured. This manipulation was designed to dissociate the strategic component of task performance from the memory-load component. Mild medicated patients with PD were impaired only on the structured versions of the verbal working memory tasks. The analogous deficit in the spatial working memory was less pronounced. These findings are in agreement with the hypothesis that working memory deficits in PD reflect mainly the executive component of the tasks and that the deficits may be at least partly modality-independent. (shrink)

Clinical responses to dopamine replacement therapy for individuals with Parkinson’s disease are often difficult to predict. We characterized changes in MDS-UPDRS motor factor scores resulting from a short-duration L-Dopa response, and investigated how the inter-subject clinical differences could be predicted from motor cortical magnetoencephalography. MDS-UPDRS motor factor scores and resting-state MEG recordings were collected during SDR from twenty individuals with a PD diagnosis. We used a novel subject-specific strategy based on linear support vector machines to quantify motor cortical oscillatory (...) frequency profiles that best predicted medication state. Motor cortical profiles differed substantially across individuals and showed consistency across multiple data folds. There was a linear relationship between classification accuracy and SDR of lower limb bradykinesia, although this relationship did not persist after multiple comparison correction, suggesting that combinations of spectral power features alone are insufficient to predict clinical state. Factor score analysis of therapeutic response and novel subject-specific machine learning approaches based on subject-specific neuroimaging provide tools to predict outcomes of therapies for PD. (shrink)

IntroductionCognitive impairment is a highly prevalent non-motor feature of Parkinson’s disease. A better understanding of the underlying pathophysiology may help in identifying therapeutic targets to prevent or treat dementia. This study sought to identify metabolic alterations in the prefrontal cortex, a key region for cognitive functioning that has been implicated in cognitive dysfunction in PD.MethodsProton Magnetic Resonance Spectroscopy was used to investigate metabolic changes in the PFC of a cohort of cognitively normal individuals without PD, as well as PD (...) participants with either normal cognition, mild cognitive impairment, or dementia. Ratios to Creatine resonance were obtained for glutamate, glutamine and glutamate combined, N-acetylaspartate, myoinositol, and total choline, and correlated with cognitive scores across multiple domains administered to the PD participants only.ResultsWhen individuals retain cognitive capabilities, the presence of Parkinson’s disease does not create metabolic disturbances in the PFC. However, when cognitive symptoms are present, PFC Glu/Cre ratios decrease with significant differences between the PD-NC and PPD groups. In addition, Glu/Cre ratios and memory scores were marginally associated, but not after Bonferroni correction.ConclusionThese preliminary findings indicate that fluctuations in prefrontal glutamate may constitute a biomarker for the progression of cognitive impairments in PD. We caution for larger MRS investigations of carefully defined PD groups. (shrink)

Professor Parkinson in his lecture on ‘The Translation Theory of Understanding’ discusses two stages in the development of a false but influential tradition which he finds common to Locke's Essay Concerning Human Understanding and Professor George Steiner's After Babel. He is not, of course, alleging any direct historical influence of the one on the other; neither is he principally addressing Steiner's book as a whole, but rather the account of understanding upon which it appears to be founded. I should (...) like to take his paper as the starting-point for my own, but begin from a somewhat broader view than he does of the legacy of Locke. With Parkinson's constructive position I have no quarrel, and I shall not address myself directly to it. (shrink)

Background: Parkinson’s disease is a neurodegenerative disease in which the progressive loss of dopaminergic neurons leads to initially sporadic and eventually widespread damage of the nervous system resulting in significant musculoskeletal and cognitive deterioration. Loss of motor function alongside increasing cognitive impairment is part of the natural disease progression. Gait is often considered an automatic activity; however, walking is the result of a delicate balance of multiple systems which maintain the body’s center of mass over an ever-changing base of (...) support. It is a complex motor behavior that requires components of attention and memory to prevent falls and injury. In addition, evidence points to the critical role of salient visual information to gait adaptability. There is a growing understanding that treatment for PD needs to address movement as it occurs naturally and walking needs to be practiced in more complex environments than traditional therapy has provided.MethodsIn this single-blinded randomized-controlled pilot study, an immersive treadmill training was piloted to determine feasibility and preliminary efficacy on gait and cognition in people with PD. Eighteen participants with Hoehn and Yahr stages I-III PD were randomized to either an intervention or a waitlist control group. Following baseline data collection, the intervention group trained for 30 min, three times/week for 4 weeks on a split belt treadmill combined with a first-person immersive video game targeting visuospatial skills and working memory. Assessment was repeated after 4 weeks of training for the experimental group and 1-month after baseline for the control group. Primary motor outcomes were captured with the APDM Opal sensors during 6 MWT, TUG, and TUG Cognitive. Secondary outcomes of cognition were measured with the Montreal Cognitive Assessment, Verbal Fluency and the Symbol Digit Modality Test. Within subject differences were calculated using the Wilcoxon Signed Ranked Test and between subject comparisons were analyzed using the Mann Whitney U-test.ResultsThis novel treadmill training program was well-tolerated with all participants in the intervention group completing 4 weeks of training three times a week without any adverse effects. After immersive cognitive motor training, the experimental group made clinically relevant improvements in gait speed and walking distance during the 6 MWT while members of the control group showed no change or decreased gait speed and walking distance over the 1-month trial. In addition, the experimental group demonstrated significant improvement for the TUG Cognitive and those changes were greater than the control group. The experimental group also improved scores on MoCA and SDMT cognitive outcome measures while the control group did not.ConclusionThe use of immersive gaming technology to engage specific areas of cognition related to gait is feasible in PD. The treadmill training program paired with a customized interactive video game improved walking velocity in addition to non-significant but consistent improvements in other gait measures and cognitive performance in participants with early to mid-stage PD. (shrink)

Dementia accompanies aging in certain susceptible individuals. The chemical function of the brain remains normal, but certain neurotransmitter-selective diseases, such as Parkinson's disease, Huntington's disease, and Alzheimer's disease occur more commonly with age.There are at least two issues troubling researchers of senile dementia at the moment. One is the contribution of cell death, as opposed to selective neuronal atrophy, to the pathology of degenerative disorders. The other is how early the onset of dementia might be detected. The resolution of (...) such issues is important for the design of therapies for the common and most serious chronic, rather than acute, neurodegenerative disease.Alzheimer's disease is one of the most devastating neurological disorders. The ethical debate is often related to when human biological life ceases or when a person ceases to exist. If the elder is still a person, he/she is no more the same person. Huntington's disease is inherited as a highly penetrant, autosomal dominant neuronal disorder. A genetic test can accurately predict a person's risk and that of the children. As the knowledge of the genetic basis is increasing and prenatal diagnosis gets easier, the possibilities to avoid child disorders will become greater, but genetic testing raises problematic ethical issues. Ethical action involves the right to know and the right not to know, it involves freedom of choice and freedom implies knowledge. It is ethical that relatives in age of procreation should be informed. In any case, efficacy and safety of the procedure, the risk-benefit ratio for a particular disease must be judged to be acceptable and understood through informed consent by the patient or the family or both. (shrink)

Humans' voice offers the widest variety of motor phenomena of any human activity. However, its clinical evaluation in people with movement disorders such as Parkinson's disease lags behind current knowledge on advanced analytical automatic speech processing methodology. Here, we use deep learning-based speech processing to differentially analyze voice recordings in 14 people with PD before and after dopaminergic medication using personalized Convolutional Recurrent Neural Networks and Phone Attribute Codebooks. p-CRNN yields an accuracy of 82.35% in the binary classification of (...) ON and OFF motor states at a sensitivity/specificity of 0.86/0.78. The PAC-based approach's accuracy was slightly lower with 73.08% at a sensitivity/specificity of 0.69/0.77, but this method offers easier interpretation and understanding of the computational biomarkers. Both p-CRNN and PAC provide a differentiated view and novel insights into the distinctive components of the speech of persons with PD. Both methods detect voice qualities that are amenable to dopaminergic treatment, including active phonetic and prosodic features. Our findings may pave the way for quantitative measurements of speech in persons with PD. (shrink)

Deep brain stimulation is a well-established therapy for the motor symptoms of Parkinson’s disease, but there remains an opportunity to improve symptom relief. The temporal pattern of stimulation is a new parameter to consider in DBS therapy, and we compared the effectiveness of Temporally Optimized Patterned Stimulation to standard DBS at reducing the motor symptoms of PD. Twenty-six subjects with DBS for PD received three different patterns of stimulation while on medication and using stimulation parameters optimized for standard DBS. (...) Side effects and motor symptoms were assessed after 30 min of stimulation with each pattern. Subjects experienced similar types of side effects with TOPS and standard DBS, and TOPS were well-tolerated by a majority of the subjects. On average, the most effective TOPS was as effective as standard DBS at reducing the motor symptoms of PD. In some subjects a TOPS pattern was the most effective pattern. Finally, the TOPS pattern with low average frequency was found to be as effective or more effective in about half the subjects while substantially reducing estimated stimulation energy use. TOPS DBS may provide a new programing option to improve DBS therapy for PD by improving symptom reduction and/or increasing energy efficiency. Optimizing stimulation parameters specifically for TOPS DBS may demonstrate further clinical benefit of TOPS DBS in treating the motor symptoms of Parkinson’s disease. (shrink)

Professor Parkinson in his lecture on ‘The Translation Theory of Understanding’ discusses two stages in the development of a false but influential tradition which he finds common to Locke's Essay Concerning Human Understanding and Professor George Steiner's After Babel. He is not, of course, alleging any direct historical influence of the one on the other; neither is he principally addressing Steiner's book as a whole, but rather the account of understanding upon which it appears to be founded. I should (...) like to take his paper as the starting-point for my own, but begin from a somewhat broader view than he does of the legacy of Locke. With Parkinson's constructive position I have no quarrel, and I shall not address myself directly to it. (shrink)

The phenomenological effects of deep brain stimulation (DBS) on the self of the patient remains poorly understood and under described in the literature, despite growing evidence that a significant number of patients experience postoperative neuropsychiatric changes. To address this lack of phenomenological evidence, we conducted in-depth, semistructured interviews with 17 patients with Parkinson's disease who had undergone DBS. Exploring the subjective character specific to patients' experience of being implanted gives empirical and conceptual understanding of the potential phenomenon of DBS-induced (...) self-estrangement. Our study concluded that (1) the more patients preoperatively felt alienated by their illness, the more they experienced postoperative self-estrangement, and (2) the notion of self-estrangement seems to exist in association with certain common qualitative characters, namely, loss of control, which reflects a deteriorative estrangement, and distorted perception of capacities, which reveals a restorative estrangement. These findings indicate that subjective self-reports help us to understand some aspects of the potential phenomenon of DBS-induced self-estrangement. (shrink)

In “Potential Subjects’ Responses to an Ethics Questionnaire in a Phase I Study of Deep-Brain Stimulation in Early Parkinson’s Disease,” Finder, Bliton, Gill, Davis, Konrad, and Charles undertake informed consent research on what they describe as a Phase I trial of deep brain stimulation (DBS) for Parkinson’s disease. We argue that the authors should have more carefully characterized the nature of the DBS study at the start of their clinical study.

Since their discovery over two decades ago, the molecular and cellular functions of the NIPSNAP family of proteins (NIPSNAPs) have remained elusive until recently. NIPSNAPs interact with a variety of mitochondrial and cytoplasmic proteins. They have been implicated in multiple cellular processes and associated with different physiologic and pathologic conditions, including pain transmission, Parkinson's disease, and cancer. Recent evidence demonstrated a direct role for NIPSNAP1 and NIPSNAP2 proteins in regulation of mitophagy, a process that is critical for cellular health (...) and maintenance. Importantly, NIPSNAPs contain a 110 amino acid domain that is evolutionary conserved from mammals to bacteria. However, the molecular function of the conserved NIPSNAP domain and its potential role in mitophagy have not been explored. It stands to reason that the highly conserved NIPSNAP domain interacts with a substrate that is ubiquitously present across all species and can perhaps act as a sensor for mitochondrial health. (shrink)

Recurrent, unvarying, and seemingly purposeless patterns of action and cognition are part of normal development, but also feature prominently in several neuropsychiatric conditions. Repetitive stereotyped behaviors can be viewed as exaggerated forms of learned habits and frequently correlate with alterations in motor, limbic, and associative basal ganglia circuits. However, it is still unclear how altered basal ganglia feedback signals actually relate to the phenomenological variability of RSBs. Why do behaviorally overlapping phenomena sometimes require different treatment approaches−for example, sensory shielding strategies (...) versus exposure therapy for autism and obsessive-compulsive disorder, respectively? Certain clues may be found in recent models of basal ganglia function that extend well beyond action selection and motivational control, and have implications for sensorimotor integration, prediction, learning under uncertainty, as well as aesthetic learning. In this paper, we systematically compare three exemplary conditions with basal ganglia involvement, obsessive-compulsive disorder, Parkinson’s disease, and autism spectrum conditions, to gain a new understanding of RSBs. We integrate clinical observations and neuroanatomical and neurophysiological alterations with accounts employing the predictive processing framework. Based on this review, we suggest that basal ganglia feedback plays a central role in preconditioning cortical networks to anticipate self-generated, movement-related perception. In this way, basal ganglia feedback appears ideally situated to adjust the salience of sensory signals through precision weighting of new sensory information, relative to the precision of predictions based on prior generated models. Accordingly, behavioral policies may preferentially rely on new data versus existing knowledge, in a spectrum spanning between novelty and stability. RSBs may then represent compensatory or reactive responses, respectively, at the opposite ends of this spectrum. This view places an important role of aesthetic learning on basal ganglia feedback, may account for observed changes in creativity and aesthetic experience in basal ganglia disorders, is empirically testable, and may inform creative art therapies in conditions characterized by stereotyped behaviors. (shrink)

This paper explores structuralism as a way to model theories from scientific practice. As a case study I analyzed a theory about the dynamics of the basal ganglia, a part of the brain that is involved in Parkinson's disease. After introducing the case study I explore how to structurally represent qualitative assumptions about disease, intervention and dynamical systems in general. I further explicate the structure of the basal ganglia theory in detail, how it explains Parkinson's disease and how (...) it implies treatments. I close with a consideration of how a structuralist representation could be useful in practice to explore and develop theories with the aid of a computer. (shrink)

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of movement disorders including Parkinson's Disease. Despite its therapeutic benefits, STN-DBS has been associated with adverse effects on mood and cognition. Specifically, apathy, which is defined as a loss of motivation, has been reported to emerge or to worsen following STN-DBS. However, it is often challenging to disentangle the effects of STN-DBSper sefrom concurrent reduction of dopamine replacement therapy, from underlying PD pathology or from (...) disease progression. To this end, pre-clinical models allow for the dissociation of each of these factors, and to establish neural substrates underlying the emergence of motivational symptoms following STN-DBS. Here, we performed a systematic analysis of rodent studies assessing the effects of STN-DBS on reward seeking, reward motivation and reward consumption across a variety of behavioral paradigms. We find that STN-DBS decreases reward seeking in the majority of experiments, and we outline how design of the behavioral task and DBS parameters can influence experimental outcomes. While an early hypothesis posited that DBS acts as a “functional lesion,” an analysis of lesions and inhibition of the STN revealed no consistent pattern on reward-related behavior. Thus, we discuss alternative mechanisms that could contribute to the amotivational effects of STN-DBS. We also argue that optogenetic-assisted circuit dissection could yield important insight into the effects of the STN on motivated behavior in health and disease. Understanding the mechanisms underlying the effects of STN-DBS on motivated behavior-will be critical for optimizing the clinical application of STN-DBS. (shrink)